1. Field of the Invention
The present invention relates to a magnetic resonance force microscope (MRFM) for performing magnetic resonance force imaging of a sample.
2. Description of Related Art
A magnetic resonance force microscope (MRFM) is an instrument that combines the techniques of a magnetic resonance imaging (MRI) instrument using a magnetic resonance technology that is a conventional technology with the techniques of an atomic force microscope (AFM) capable of imaging atoms on sample surfaces. It is anticipated that the MRFM is an MRI instrument producing a spatial resolution at atomic level. The purpose of the utilization is defined to be a quantitative analysis consisting chiefly of imaging and analyzing three-dimensional structures of extremely small samples, such as a single gene, proteins, and biological molecules. MRFM apparatus are currently being developed by some groups and are in a developmental stage. It is said that the highest spatial resolution attained today is 20 nm. MRFM is described in U.S. Pat. No. 5,266,896; Japanese Patent Publication No. H7-69289; Proceedings of the Magnetic Society of Japan, Vol. 22, No. 1, p. 19 (1998); and Journal of Applied Physics, Vol. 79, p. 1881 (1996)
FIG. 1 schematically shows the configuration of an MRFM apparatus consisting of laser light passed through an optical fiber 1, a cantilever 2 receiving the laser light, and a sample stage 3 on which a sample 4 is placed. The stage 3 operates as a scanner. Meanwhile, elements necessary for magnetic resonance include an RF (radio-frequency) coil 5 and an external static magnetic field (not shown). A magnetic field gradient indispensable for MRI (magnetic resonance imaging) is produced by a magnetic field that is quite inhomogeneous spatially. This inhomogeneous field is set up by a magnetic tip 6 that is mounted at the tip of the cantilever 2 and made of a magnetic material (including a permanent magnet) with high magnetic permeability.
The operation of the MRFM apparatus is now described. A magnetic resonance phenomenon within the MRFM apparatus is produced when resonant conditions are satisfied. The resonant conditions are uniquely determined by the relationship between a static magnetic field inside the sample and the frequency of the RF magnetic field applied by the RF coil 5. The static magnetic field inside the sample is defined to be the sum of the externally applied magnetic field and the magnetic field produced by the magnetic tip 6.
When the resonant conditions do not hold, the cantilever 2 feels a magnetic field given by the product of the magnetization of the sample polarized by the aforementioned static magnetic field and the magnetic field gradient produced by the magnetic tip 6, and has been displaced from the position assumed in the thermal equilibrium state that is defined when neither magnetic field nor magnetic field gradient is present.
When the resonant conditions hold, the reduced polarization magnetization weakens the magnetic force, forcing the cantilever 2 to return toward the position assumed in the thermal equilibrium state. The variation in the magnetic force produced at this time is referred to as a magnetic resonance force.
The physical quantity measured in MRFM is this amount of displacement of the amplitude of the cantilever. The amount of displacement is measured using an optical interferometer or optical beam deflection. A distribution of the intensities of magnetic resonance forces at various locations can be obtained by scanning the relative position of the magnetic tip 6 to the sample 4. A real space image is reproduced by computer-processing the distribution of the intensities of the magnetic resonance forces while taking account of known magnetic field distributions and magnetic field gradient distributions.
MRI can measure a three-dimensional distribution of the numbers of electron spins or certain atomic nuclear spins or magnitudes of spin magnetizations at positions inside a sample. However, if an MRI image is obtained by imaging only a portion containing spins of interest, it may not be possible to locate the position of this portion within the whole sample or to identify to what tissue that portion belongs.
FIG. 2A is a view of a sample 4 placed on the surface of the scanner (sample stage), as viewed from a direction perpendicular to the surface. It is assumed that the sample 4 is made of some materials that are different in composition and morphology. It is also assumed that spins capable of being observed by MRI are contained only in a portion 8 indicated by arrow 7.
FIG. 2B is an image 8′ that would be acquired when the sample 4 is imaged by MR. It is now assumed that the user wants to provide an estimate from an MRI image alone as to where the portion producing the image is located within the sample. For this purpose, it is necessary to grasp the shapes of the individual components of the material in advance. Furthermore, to allow the user to correlate these shapes with the obtained MRI image and to make a choice, the MRI image must reveal a particular shape or contain a characteristic portion representing the sample 4.
Comparison of FIGS. 2B and 2B makes it possible to conclude that any one of the six horizontally elongated materials 8-13 is contained in the sample 4 in FIG. 2A. However, it is impossible to determine which one of them is exactly responsible. That is, there remains room for improvement for understanding of MRI images.
If an image of the whole sample taken in the same field of view of an MRI image irrespective of the presence or absence of spins of interest is derived, in addition to the MRI image, the MRI image can be understood more deeply.
FIG. 2C shows an image that is anticipated to be acquired when the sample is imaged by such an imaging technique. It is also assumed that the field of view and the observer's eye are identical with their counterparts in FIG. 2B. If an image as shown in FIG. 2C is obtained, it is possible to locate the position of the portion 8′ imaged as shown in the FIG. 2B within FIG. 2C by superimposing the obtained image on the image of FIG. 2B.